WEDNESDAY, Aug. 17 (HealthDay News) -- Generalized pustular psoriasis is associated with mutated interleukin-36-receptor antagonist (interleukin-36Ra) structure and unregulated production of inflammatory cytokines, according to a study published in the Aug. 18 issue of the New England Journal of Medicine.
Slaheddine Marrakchi, M.D., Ph.D., from the Sfax University in Tunisia, and colleagues conducted homozygosity mapping and direct sequencing in members of nine Tunisian multiplex families with autosomal recessive generalized pustular psoriasis to investigate the impact of mutations on protein expression and conformation, stability, and function.
The investigators found that the occurrence of the disease was significantly linked to an interval of 1.2 megabases on chromosome 2q13-q14.1, and a homozygous missense mutation in IL36RN that resulted in the substitution of proline for leucine at amino acid position 27 (L27P) of the interleukin-36Ra protein. The stability of the interleukin-36Ra protein and its affinity for the interleukin-1 receptor-like 2 receptor were both affected by the L27P mutation. Compared to the nonvariant interleukin-36Ra, L27P variant showed poor expression and less potency in inhibiting a cytokine-induced response in an interleukin-8 reporter assay, subsequently enhancing inflammatory production by keratinocytes.
"Aberrant interleukin-36Ra structure and function lead to unregulated secretion of inflammatory cytokines and generalized pustular psoriasis," the authors write.
Several authors disclosed financial relationships with various pharmaceutical companies.
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